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Objective: We investigated the relationship between personal relative deprivation (PRD)-resentment from the belief that one is worse off than people who are similar to oneself-and locus of control., Background: Research has yet to comprehensively investigate whether PRD is associated with a tendency to favor external (vs. internal) explanations for self- and other-relevant outcomes., Method: Eight studies (N total  = 6729) employed cross-sectional, experimental, and (micro)longitudinal designs and used established trait and state measures of PRD and loci of control., Results: Participants higher in PRD adopted more external (vs. internal) explanations for others' outcomes while controlling for socio-demographics (e.g., socioeconomic status; Studies 1-4). This relationship was mediated by a lowered sense of personal control (Study 1) and evident in a cross-national sample of participants in Asia (Study 2). PRD is more robustly associated with external than internal explanations for self and other-relevant outcomes (Studies 5-8), and within-person changes in PRD are positively associated with within-person changes in external explanations (month-to-month and day-to-day; Studies 7-8)., Conclusions: PRD is positively associated with external locus of control independent of socioeconomic status, within and between people, and across cultures. This research highlights the implications of PRD for people's construal of the causal forces that govern their lives., (© 2024 The Author(s). Journal of Personality published by Wiley Periodicals LLC.)

Although the need for social connection is fundamental, people approach this need through different strategies. Drawing from life history theory, the current research explored whether individuals' early-life experiences are associated with narrow/deep (depth), or broad/shallow (breadth) approach to social relationships. Three studies revealed that participants' childhood socioeconomic status (SES) interacts with perception of economic instability to create diverging preferences in social relationship pattern. Specifically, when economic instability was salient (chronic belief, Study 1; experimentally primed, Studies 2 and 3), individuals from lower-SES childhood preferred a narrower and deeper social network, whereas those from higher-SES childhood preferred a broader and shallower network. Taken together, the present research offers a novel understanding of depth- versus breadth-focused approach to social relationships from the perspective of life history theory.

Throughout the 21st century, economic inequality is predicted to increase as we face new challenges, from changes in the technological landscape to the growing climate crisis. It is crucial we understand how these changes in inequality may affect how people think and behave. We propose that economic inequality threatens the social fabric of society, in turn increasing moralization-that is, the greater tendency to employ or emphasize morality in everyday life-as an attempt to restore order and control. Using longitudinal data from X, formerly known as Twitter, our first study demonstrates that high economic inequality is associated with greater use of moral language online (e.g. the use of words such as "disgust", "hurt", and "respect'). Study 2 then examined data from 41 regions around the world, generally showing that higher inequality has a small association with harsher moral judgments of people's everyday actions. Together these findings demonstrate that economic inequality is linked to the tendency to see the world through a moral lens., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

People cooperate every day in ways that range from largescale contributions that mitigate climate change to simple actions such as leaving another individual with choice - known as social mindfulness. It is not yet clear whether and how these complex and more simple forms of cooperation relate. Prior work has found that countries with individuals who made more socially mindful choices were linked to a higher country environmental performance - a proxy for complex cooperation. Here we replicated this initial finding in 41 samples around the world, demonstrating the robustness of the association between social mindfulness and environmental performance, and substantially built on it to show this relationship extended to a wide range of complex cooperative indices, tied closely to many current societal issues. We found that greater social mindfulness expressed by an individual was related to living in countries with more social capital, more community participation and reduced prejudice towards immigrants. Our findings speak to the symbiotic relationship between simple and more complex forms of cooperation in societies., (© 2022. The Author(s).)

The COVID-19 pandemic caused drastic social changes for many people, including separation from friends and coworkers, enforced close contact with family, and reductions in mobility. Here we assess the extent to which people's evolutionarily-relevant basic motivations and goals-fundamental social motives such as Affiliation and Kin Care-might have been affected. To address this question, we gathered data on fundamental social motives in 42 countries ( N  = 15,915) across two waves, including 19 countries ( N   =  10,907) for which data were gathered both before and during the pandemic (pre-pandemic wave: 32 countries, N  = 8998; 3302 male, 5585 female; M age   =  24.43, SD  = 7.91; mid-pandemic wave: 29 countries, N  = 6917; 2249 male, 4218 female; M age   =  28.59, SD  = 11.31). Samples include data collected online (e.g., Prolific, MTurk), at universities, and via community sampling. We found that Disease Avoidance motivation was substantially higher during the pandemic, and that most of the other fundamental social motives showed small, yet significant, differences across waves. Most sensibly, concern with caring for one's children was higher during the pandemic, and concerns with Mate Seeking and Status were lower. Earlier findings showing the prioritization of family motives over mating motives (and even over Disease Avoidance motives ) were replicated during the pandemic. Finally, well-being remained positively associated with family-related motives and negatively associated with mating motives during the pandemic, as in the pre-pandemic samples. Our results provide further evidence for the robust primacy of family-related motivations even during this unique disruption of social life., Competing Interests: None., (© 2022 Elsevier Inc. All rights reserved.)

Previous studies on self-enhancement bias used self-report measures to investigate individual and cultural differences in well-being. In the current research, we took a behavioral approach to analyze positive and negative perception tendencies between European Canadians, Asian Canadians and Koreans. In Study 1 and 2, participants were asked to bet on their expectation of success on a given task and then perform the task. The betting behaviors and actual performance were used to quantify positive and negative perception tendencies. In Study 1, we did not find cultural differences in positive and negative illusions. Positive self-perceptions were also not associated with higher self-reported well-being. In Study 2, we employed the same research design as Study 1, and we included a measure of perceived desirability to examine whether perceived desirability of the performance tasks are related to the two illusions indices. The results from Study 2 replicated the findings from Study 1, and perceived desirability did not influence the results. Our findings suggest that North Americans do not always exhibit more positive self-perceptions than Asians, suggesting that North Americans do not always view the self through rose-colored lenses., Competing Interests: The authors have declared that no competing interests exist.

How does psychology vary across human societies? The fundamental social motives framework adopts an evolutionary approach to capture the broad range of human social goals within a taxonomy of ancestrally recurring threats and opportunities. These motives-self-protection, disease avoidance, affiliation, status, mate acquisition, mate retention, and kin care-are high in fitness relevance and everyday salience, yet understudied cross-culturally. Here, we gathered data on these motives in 42 countries (N = 15,915) in two cross-sectional waves, including 19 countries (N = 10,907) for which data were gathered in both waves. Wave 1 was collected from mid-2016 through late 2019 (32 countries, N = 8,998; 3,302 male, 5,585 female; M age  = 24.43, SD = 7.91). Wave 2 was collected from April through November 2020, during the COVID-19 pandemic (29 countries, N = 6,917; 2,249 male, 4,218 female; M age  = 28.59, SD = 11.31). These data can be used to assess differences and similarities in people's fundamental social motives both across and within cultures, at different time points, and in relation to other commonly studied cultural indicators and outcomes., (© 2022. The Author(s).)

Happiness is a valuable experience, and societies want their citizens to be happy. Although this societal commitment seems laudable, overly emphasizing positivity (versus negativity) may create an unattainable emotion norm that ironically compromises individual well-being. In this multi-national study (40 countries; 7443 participants), we investigate how societal pressure to be happy and not sad predicts emotional, cognitive and clinical indicators of well-being around the world, and examine how these relations differ as a function of countries' national happiness levels (collected from the World Happiness Report). Although detrimental well-being associations manifest for an average country, the strength of these relations varies across countries. People's felt societal pressure to be happy and not sad is particularly linked to poor well-being in countries with a higher World Happiness Index. Although the cross-sectional nature of our work prohibits causal conclusions, our findings highlight the correlational link between social emotion valuation and individual well-being, and suggest that high national happiness levels may have downsides for some., (© 2022. The Author(s).)

What kind of life do people want? In psychology, a good life has typically been conceptualized in terms of either hedonic or eudaimonic well-being. We propose that psychological richness is another neglected aspect of what people consider a good life. In study 1 (9-nation cross-cultural study), we asked participants whether they ideally wanted a happy, a meaningful, or a psychologically rich life. Roughly 7 to 17% of participants chose the psychologically rich life. In study 2, we asked 1611 Americans and 680 Koreans what they regret most in their lives; then, if they could undo or reverse the regretful event, whether their lives would have been happier, more meaningful, or psychologically richer as a result. Roughly 28% of Americans and 35% of Koreans reported their lives would have been psychologically richer. Together, this work provides a foundation for the study of psychological richness as another dimension of a good life., Competing Interests: Conflict of InterestThe authors declare that there are no conflicts of interest., (© The Society for Affective Science 2020.)

What motives do people prioritize in their social lives? Historically, social psychologists, especially those adopting an evolutionary perspective, have devoted a great deal of research attention to sexual attraction and romantic-partner choice (mate seeking). Research on long-term familial bonds (mate retention and kin care) has been less thoroughly connected to relevant comparative and evolutionary work on other species, and in the case of kin care, these bonds have been less well researched. Examining varied sources of data from 27 societies around the world, we found that people generally view familial motives as primary in importance and mate-seeking motives as relatively low in importance. Compared with other groups, college students, single people, and men place relatively higher emphasis on mate seeking, but even those samples rated kin-care motives as more important. Furthermore, motives linked to long-term familial bonds are positively associated with psychological well-being, but mate-seeking motives are associated with anxiety and depression. We address theoretical and empirical reasons why there has been extensive research on mate seeking and why people prioritize goals related to long-term familial bonds over mating goals. Reallocating relatively greater research effort toward long-term familial relationships would likely yield many interesting new findings relevant to everyday people's highest social priorities.

Background: Research in the US found that gratitude increases happiness. We conducted three studies to examine whether gratitude increases happiness among Koreans, as well., Methods: Participants were randomly assigned to a gratitude or a control condition in Studies 1 and 2, and into a gratitude toward someone important or a gratitude toward own health condition in Study 3. Their moods were then measured., Results: Gratitude writing marginally significantly evoked indebtedness among Korean students (Study 1, N = 336) but not among American students (Study 2, N = 219). Equally important, even among Americans, those who wrote about their gratitude toward someone important reported feeling indebtedness marginally more than those who wrote about their gratitude toward something or someone not that important. In Study 3 (N = 181), American participants, randomly assigned to write about their gratitude toward someone important, reported not only more gratitude but also more indebtedness than those assigned to write about their gratitude toward their own health., Conclusions: Taken together, these studies suggest that gratitude evokes indebtedness when gratitude is about someone important., (© 2018 The International Association of Applied Psychology.)

The present study examined cultural differences in the act of sharing positive events with others, called capitalization attempts. The first three studies tested whether capitalization attempts differ between two cultures using multiple methods: self-reports (Study 1), children's storybooks (Study 2), and Facebook (Study 3). We found that Koreans are less likely to share their positive events with others than European Americans. Study 4 further examined the antecedents and consequences of capitalization attempts. We replicated the earlier findings that Koreans are hesitant to share their positive events and demonstrated that this is because Koreans are more concerned about the potential negative consequences for social relationships. Moreover, we found that the cultural differences in capitalization attempts partly account for mean-level differences in well-being between cultures. Implications for capitalization, culture, and well-being are discussed.

Does close distance increase liking for a social object? In a preliminary sociogram task, an association between proximity and intimacy was found in drawings of self and others. In three experimental studies, male participants consistently preferred female targets who were (actually or appeared to be) close than far from them. Distance was manipulated through various means-sitting distance (Study 2), presenting two facial images separately to each eye by a stereoscopic device (Study 3), or a video clip (Study 4). This effect was stronger among those with deprived social needs and occurred in part because close (vs. far) targets seemed psychologically more accessible to the perceiver. Our findings offer rare experimental evidence for the empirically challenged propinquity effect and provide new insights on how distance shapes inner experience.

The current research developed and validated a Korean-translated version of the Personal Relative Deprivation Scale (PRDS). The PRDS measures individual differences in people's tendencies to feel resentful about what they have compared to what other people like them have. Across 2 studies, Exploratory Factor Analyses revealed that the two reverse-worded items from the original PRDS did not load onto the primary factor for the Korean-translated PRDS. A reduced 3-item Korean PRDS, however, showed good convergent validity. Replicating previous findings using Western samples, greater tendencies to make social comparisons of abilities (but not opinions) were associated with higher PRDS (Studies 1 and 2), and participants scoring higher on the 3-item Korean PRDS were more materialistic (Studies 1 and 2), reported worse physical health (Study 1), had lower self-esteem (Study 2) and experienced higher stress (Study 2).

Background: Thymidine kinase 1 (TK1) is a cell cycle-regulated enzyme with peak expression in the S phase during DNA synthesis, and it is an attractive biomarker of cell proliferation. Serum TK1 activity has demonstrated prognostic value in patients with early-stage breast cancer. Because cyclin-dependent kinase 4/6 (CDK4/6) inhibitors prevent G 1 /S transition, we hypothesized that serum TK1 could be a biomarker for CDK4/6 inhibitors. We examined the drug-induced change in serum TK1 as well as its correlation with change in tumor Ki-67 levels in patients enrolled in the NeoPalAna trial (ClinicalTrials.gov identifier NCT01723774)., Methods: Patients with clinical stage II/III estrogen receptor-positive (ER+)/HER2-negative breast cancer enrolled in the NeoPalAna trial received an initial 4 weeks of anastrozole, followed by palbociclib on cycle 1, day 1 (C1D1) for four 28-day cycles, unless C1D15 tumor Ki-67 was > 10%, in which case patients went off study owing to inadequate response. Surgery occurred following 3-5 weeks of washout from the last dose of palbociclib, except in eight patients who received palbociclib (cycle 5) continuously until surgery. Serum TK1 activity was determined at baseline, C1D1, C1D15, and time of surgery, and we found that it was correlated with tumor Ki-67 and TK1 messenger RNA (mRNA) levels., Results: Despite a significant drop in tumor Ki-67 with anastrozole monotherapy, there was no statistically significant change in TK1 activity. However, a striking reduction in TK1 activity was observed 2 weeks after initiation of palbociclib (C1D15), which then rose significantly with palbociclib washout. At C1D15, TK1 activity was below the detection limit (<20 DiviTum units per liter Du/L) in 92% of patients, indicating a profound effect of palbociclib. There was high concordance, at 89.8% (95% CI: 79.2% - 96.2%), between changes in serum TK1 and tumor Ki-67 in the same direction from C1D1 to C1D15 and from C1D15 to surgery time points. The sensitivity and specificity for the tumor Ki-67-based response by palbociclib-induced decrease in serum TK1 were 94.1% (95% CI 86.2% - 100%) and 84% (95% CI 69.6% -98.4%), respectively. The κ-statistic was 0.76 (p < 0.001) between TK1 and Ki-67, indicating substantial agreement., Conclusions: Serum TK1 activity is a promising pharmacodynamic marker of palbociclib in ER+ breast cancer, and its value in predicting response to CDK4/6 inhibitors warrants further investigation., Trial Registration: ClinicalTrials.gov, NCT01723774. Registered on 6 November 2012.

Pancreatic cancer, the fourth leading cause of cancer death in the United States, has a negative prognosis because metastasis occurs before symptoms manifest. Leiodermatolide, a polyketide macrolide with antimitotic activity isolated from a deep water sponge of the genus Leiodermatium, exhibits potent and selective cytotoxicity toward the pancreatic cancer cell lines AsPC-1, PANC-1, BxPC-3, and MIA PaCa-2, and potent cytotoxicity against skin, breast and colon cancer cell lines. Induction of apoptosis by leiodermatolide was confirmed in the AsPC-1, BxPC-3 and MIA PaCa-2 cells. Leiodermatolide induces cell cycle arrest but has no effects on in vitro polymerization or depolymerization of tubulin alone, while it enhances polymerization of tubulin containing microtubule associated proteins (MAPs). Observations through confocal microscopy show that leiodermatolide, at low concentrations, causes minimal effects on polymerization or depolymerization of the microtubule network in interphase cells, but disruption of spindle formation in mitotic cells. At higher concentrations, depolymerization of the microtubule network is observed. Visualization of the growing microtubule in HeLa cells expressing GFP-tagged plus end binding protein EB-1 showed that leiodermatolide stopped the polymerization of tubulin. These results suggest that leiodermatolide may affect tubulin dynamics without directly interacting with tubulin and hint at a unique mechanism of action. In a mouse model of metastatic pancreatic cancer, leiodermatolide exhibited significant tumor reduction when compared to gemcitabine and controls. The antitumor activities of leiodermatolide, as well as the proven utility of antimitotic compounds against cancer, make leiodermatolide an interesting compound with potential chemotherapeutic effects that may merit further research., Competing Interests: ◆ Conflict of Interest Disclosure: Guzmán, Pitts, Linley, Winder, Baker and Wright have no conflicts of interest to disclose. Xu, Tendyke, Oestreicher, Mitsuhashi and Suh are either current or former employees of Eisai, Inc., (© 2016 UICC.)

Evidence shows that people feel mild positive moods when no strong emotional events are occurring, a phenomenon known as positive mood offset. We offer an evolutionary explanation of this characteristic, showing that it improves fertility, fecundity, and health, and abets other characteristics that were critical to reproductive success. We review research showing that positive mood offset is virtually universal in the nations of the world, even among people who live in extremely difficult circumstances. Positive moods increase the likelihood of the types of adaptive behaviors that likely characterized our Paleolithic ancestors, such as creativity, planning, mating, and sociality. Because of the ubiquity and apparent advantages of positive moods, it is a reasonable hypothesis that humans were selected for positivity offset in our evolutionary past. We outline additional evidence that is needed to help confirm that positive mood offset is an evolutionary adaptation in humans and we explore the research questions that the hypothesis generates., (© 2014 by the Society for Personality and Social Psychology, Inc.)

A general C-H functionalization method for the tagging of natural products and pharmaceuticals is described. An azide-containing sulfinate reagent allows the appendage of azidoalkyl chains onto heteroaromatics, the product of which can then be attached to a monoclonal antibody by a "click" reaction. This strategy expands the breadth of bioactive small molecules that can be linked to macromolecules in a manner that is beyond the scope of existing methods in bioconjugation to permit tagging of the "seemingly untaggable".

Investigation of the endemic Madagascan plant Uvaria sp. for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of two new acetogenins. The structures of these two compounds were elucidated on the basis of analysis of their 1D and 2D NMR spectra, circular dichroism, and mass spectrometric data, together with chemical modification. The two acetogenins display weak antiproliferative activity against the A2780 ovarian cancer, the A2058 melanoma, and the H522 lung cancer cell lines.

Investigation of the Madagascan endemic plant Ambavia gerrardii for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the three new alkaloids 8-hydroxyeupolauridine (1), 9-methoxyeupolauridine 1-oxide (2), and 11-methoxysampangine (3) and the three known alkaloids 4-6. The structures of 1 and 2 were confirmed by synthesis. Compounds 3, 4, and 6 showed moderate to good antiproliferative activities, with IC50 values of 10.3, 3.5, and 0.60 μM, respectively, against the A2780 human ovarian cancer cell line and with IC50 values of 0.57, 1.77, and 0.58 μM, respectively, against the H460 human lung cancer cell line.

Investigation of the endemic Madagascar plant Leptadenia madagascariensis Decne. (Apocynaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the four new cardenolides 1-4. The structure elucidations of these compounds were based on analyzes of their 1D and 2D NMR spectra and mass spectrometric data. The cardenolides were strongly antiproliferative to the A2780 ovarian cancer cell line, with IC(50) values of 0.18, 0.21, 0.17, and 0.29μM line, and to the H460 human lung cancer cell line, with IC(50) values of 0.16, 0.68, 0.37, and 0.48μM, respectively., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Bioassay-guided fractionation of an ethanol extract of the roots of the endemic Malagasy plant Pongamiopsis pervilleana led to the isolation of the three new compounds (2'R)-4'-hydroxyemoroidocarpan (1), pongavilleanine (3), and epipervilline (4) together with two known compounds, identified as emoroidocarpan (2) and rotenolone (5). The structures of all compounds were determined by physical, chemical, and spectroscopic evidence. The stereochemistry at C-2' of the previously reported compound emoroidocarpan was determined to be R by the observation of a negative Cotton effect at 474 nm in the CD spectrum of its osmate ester derivative. Compounds 2-5 displayed moderate antiproliferative activity against the A2780 human ovarian cancer cell line, and rotenolone also showed micromolar antiproliferative activity toward the breast cancer BT-549, prostate cancer DU 145, NSCLC NCI-H460, and colon cancer HCC-2998 cell lines.

Research has demonstrated that certain genotypes are expressed in different forms, depending on input from the social environment. To examine sensitivity to cultural norms regarding emotional support seeking as a type of social environment, we explored the behavioral expression of oxytocin receptor polymorphism (OXTR) rs53576, a gene previously related to socio-emotional sensitivity. Seeking emotional support in times of distress is normative in American culture but not in Korean culture. Consequently, we predicted a three-way interaction of culture, distress, and OXTR genotype on emotional support seeking. Korean and American participants (n = 274) completed assessments of psychological distress and emotional support seeking and were genotyped for OXTR. We found the predicted three-way interaction: among distressed American participants, those with the GG/AG genotypes reported seeking more emotional social support, compared with those with the AA genotype, whereas Korean participants did not differ significantly by genotype; under conditions of low distress, OXTR groups did not differ significantly in either cultural group. These findings suggest that OXTR rs53576 is sensitive to input from the social environment, specifically cultural norms regarding emotional social support seeking. These findings also indicate that psychological distress and culture are important moderators that shape behavioral outcomes associated with OXTR genotypes.

The present research examined the interaction between genes and culture as potential determinants of individuals' locus of attention. As the serotonin (5-HT) system has been associated with attentional focus and the ability to adapt to changes in reinforcement, we examined the serotonin 1A receptor polymorphism (5-HTR1A). Koreans and European Americans were genotyped and reported their chronic locus of attention. There was a significant interaction between 5-HTR1A genotype and culture in the locus of attention. Koreans reported attending to the field more than European Americans, and this cultural difference was moderated by 5-HTR1A. There was a linear pattern such that those homozygous for the G allele, which is associated with reduced ability to adapt to changes in reinforcement, more strongly endorsed the culturally reinforced mode of thinking than those homozygous for the C allele, with those heterozygous in the middle. Our findings suggest that the same genetic predisposition can result in divergent psychological outcomes, depending on an individual's cultural context.

Fractionation of an ethanol extract of a Madagascar collection of the leaves and fruit of Cassipourea lanceolata Tul. led to the isolation of three euphane triterpenoids 1-3. The (1)H and (13)C NMR spectra of all compounds were fully assigned using a combination of 2D NMR experiments, including COSY, TOCSY, HSQC (HMQC), HMBC and ROESY sequences. The three compounds showed weak antiproliferative activities against the A2780 human ovarian cancer cell line, with IC(50) values of 25, 25 and 32 microM, respectively., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Self-construal abstractness (SCA) refers to the degree to which people construe important bases of self-esteem in a broad, flexible, and abstract rather than a concrete and specific manner. This article hypothesized that SCA would be a unique predictor of self-esteem stability, capturing the degree to which people's most important bases of self-worth are resistant to disconfirmation. Two studies using a daily diary methodology examined relationships between SCA, daily self-esteem, and daily emotions and/or events. In Study 1, individual differences in SCA emerged as the most consistent and unique predictor of self-esteem stability. Furthermore, SCA contributed to self-esteem stability by buffering the influence of daily negative emotions on self-esteem. Study 2 manipulated SCA via a daily self-construal task and found an abstract versus concrete self-focus to buffer the influence of daily negative events on self-esteem. Implications of these findings for the study of the self and well-being are discussed.

E7974 is a synthetic analogue of the marine sponge natural product hemiasterlin. Here, we show that E7974, such as parental hemiasterlin, acts via a tubulin-based antimitotic mechanism. E7974 inhibits polymerization of purified tubulin in vitro with IC(50) values similar to those of vinblastine. In cultured human cancer cells, E7974 induces G(2)-M arrest and marked disruption of mitotic spindle formation characteristic of tubulin-targeted anticancer drugs. Extensive hypodiploid cell populations are seen in E7974-treated cells, indicating initiation of apoptosis after prolonged G(2)-M blockage. Consistent with this observation, E7974 induces caspase-3 activation and poly ADP ribose polymerase cleavage, typical biochemical markers of apoptosis. Only a short cellular exposure to E7974 is sufficient to induce maximum mitotic arrest, suggesting that E7974's antitumor effects in vivo may persist even after blood levels of the drug decrease after drug administration. Interactions of E7974 with purified tubulin were investigated using two synthetic tritiated photoaffinity analogues incorporating a benzophenone photoaffinity moiety at two different positions of the E7974 scaffold. Both analogues preferentially photolabeled alpha-tubulin, although minor binding to beta-tubulin was also detected. E7974 thus seems to share a unique, predominantly alpha-tubulin-targeted mechanism with other hemiasterlin-based compounds, suggesting that, unlike many tubulin-targeted natural products and related drugs, the hemiasterlins evolved to mainly target alpha-tubulin, not beta-tubulin subunits.

Bioassay-guided fractionation of an EtOH extract obtained from the roots of the Madagascan plant Dodonaea viscosa led to the isolation of two new antiproliferative oleanane-type triterpenoid saponins, dodoneasides A and B (1 and 2). The structures of these two new compounds were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1 and 2 showed antiproliferative activity against the A2780 human ovarian cancer cell line with IC(50) values of 0.79 and 0.70 muM, respectively.

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of Elaeodendron alluaudianum led to the isolation of two new cardenolide glycosides (1 and 2). The (1)H and (13)C NMR spectra of both compounds were fully assigned using a combination of 2D NMR experiments, including (1)H-(1)H COSY, HSQC, HMBC, and ROESY sequences. Both compounds 1 and 2 were tested against the A2780 human ovarian cancer cell line and the U937 human histiocytic lymphoma cell line assays, and showed significant antiproliferative activity with IC(50) values of 0.12 and 0.07 microM against the A2780 human ovarian cancer cell line, and 0.15 and 0.08 microM against the U937 human histiocytic lymphoma cell line, respectively.

Bioassay-guided fractionation of an ethanol extract of a Malleastrum sp. afforded three new limonoids, malleastrones A-C ( 1- 3), respectively. Each limonoid contained a rare tetranortriterpenoid skeleton. Structure elucidation of the isolates was carried out by analysis of one- and two-dimensional NMR and X-ray diffraction data. The novel isolates 1 and 2 were tested for antiproliferative activity against a panel of cancer cell lines and exhibited IC 50 values ranging from 0.19 to 0.63 microM.

Bioassay-guided fractionation of an ethanol extract of Artabotrys madagascariensis led to the isolation of the new compound artabotrene (1), two butenolides (2 and 3), and the tetracyclic triterpene polycarpol (4). Structure elucidation was determined on the basis of one and two-dimensional NMR, and absolute configuration of compounds 2-4 was verified by analysis of CD and optical rotation spectra. Two of the isolates, melodorinol (2) and acetylmelodorinol (3), were found to display antiproliferative activity against five different tumour cell lines with IC50 values ranging from 2.4 to 12 microM.

The self becomes context sensitive in service of the need to belong. When it comes to achieving personal happiness, an identity system that derives its worth and meaning excessively from its social context puts itself in a significantly disadvantageous position. This article integrates empirical findings and ideas from the self, subjective well-being, and cross-cultural literature and tries to offer insights to why East Asian cultural members report surprisingly low levels of happiness. The various cognitive, motivational, behavioral, and affective characteristics of the overly relation-oriented self are discussed as potential explanations. Implications for the study of self and culture are offered.

Bioassay-guided fractionation of an ethanol extract obtained from the Madagascar plant Elaeodendron sp. led to the isolation of two new cardenolides, elaeodendrosides T and U (1 and 2). The structures of the new compounds were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1, 3, 4, and 5 showed significant antiproliferative activity against A2780 human ovarian cancer cells with IC50 values of 0.085, 0.019, 0.19, and 0.10 microM, respectively, while compounds 2 and 6 were less active.

All individuals have multiple views of themselves. Whereas the consistency among the different aspects of identity is emphasized in Western cultures, the "multiple selves" are often viewed as coexisting realities in East Asian cultures. This research revisits the classic thesis in psychology that identity consistency is a prerequisite condition of psychological well-being. Between individuals (Study 1), people with a more consistent self-view had a more clear self-knowledge, were more assertive, and, most notably, had self-experiences that were less affected by the perspectives of others. Compared with North American participants (Study 2), Koreans viewed themselves more flexibly across situations, and their subjective well-being was less predictable from levels of identity consistency. Also, consistent individuals received positive social evaluations from others in the United States but not in Korea.

Ecologies shape cultures; cultures influence the development of personalities. There are both universal and culture-specific aspects of variation in personality. Some culture-specific aspects correspond to cultural syndromes such as complexity, tightness, individualism, and collectivism. A large body of literature suggests that the Big Five personality factors emerge in various cultures. However, caution is required in arguing for such universality, because most studies have not included emic (culture-specific) traits and have not studied samples that are extremely different in culture from Western samples.

Psychologists have not determined the defining characteristics of extraversion. In four studies, the authors tested the hypothesis that extraversion facets are linked by reward sensitivity. According to this hypothesis, only facets that reflect reward sensitivity should load on a higher order extraversion factor. This model was tested against a model in which sociability links the facets. The authors also tested the generalizability of the model in a diverse sample of participants from 39 nations, and they tested the model using widely used extraversion scales. Results of all studies indicate that only facets that reflect reward sensitivity load on a higher order extraversion factor and that this factor correlates strongly with pleasant affect. Although sociability is undoubtedly an important part of extraversion, these results suggest that extraverts' sociability may be a by-product of reward sensitivity, rather than the core feature of the trait.

We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5-benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the C3 and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at C3. Structure-activity relationships at the N1-anilidoacetamide "trigger" moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the N1-anilidoacetamide moiety. Evaluation of several analogs in an vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.

The synthesis of 1,3-disubstituted pyrrolidines 2 and their activities as type IV phosphodiesterase (PDE) inhibitors are described. Various groups were appended to the nitrogen of the pyrrolidine nucleus to enable structure-activity relationships to be assessed. Groups which render the pyrrolidine nitrogen of 2 nonbasic yielded potent PDE-IV inhibitors. Analogs of amides, carbamates, and ureas of 2 were synthesized to determine the effects that substitution on these functional groups had on PDE-IV inhibitor potency. The structural requirements for PDE-IV inhibitor potency differed among the three classes. A representative amide, carbamate, and urea (2c,d,h) were shown to be > 50-fold selective for inhibiting PDE-IV versus representative PDEs from families I-III and V. Furthermore, these same three inhibitors demonstrated potent functional activity (IC50 < 1 microM) by inhibiting tumor necrosis factor-alpha (TNF-alpha) release from lipopolysaccharide (LPS)-activated purified human peripheral blood monocytes and mouse peritoneal macrophages. These compounds were also tested orally in LPS-injected mice and demonstrated dose-dependent inhibition of serum TNF-alpha levels.